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CROI 2022 Key Aging & Comorbidities Highlights
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CROI Monday Feb 14: 5 Key Aging & Metabolic Oral Presentation Studies - (02/15/22)
1. Higher heart disease risk (myocardial infarction) for PLWH in 2010-2017 compared to people without HIV.
2. novel imaging technique provides evidence of unique arterial inflammation in PLWH on ART thought to contribute to heightened heart disease risk for PLWH.
3. Addressing the concern that PLWH have higher risk for type 2 diabetes - PLWH have higher fat tissue fibrosis & inflammation markers/pathways identified to be associated with new diabetes diagnosis in PLWH.
4. Functional impairment examined in global REPRIEVE Trial, found 36% impaired with stepwise worsening based on age & 55-59 & >60 yrs old the worst. African-American, BMI, waist circumference, transgender spectrum, Southeast Asia, ARTs relationships associated with worse outcomes. Moderate & severe functional impairment associated with increased heart disease risk.
5. Antcholinergenics drugs common used for older PLWH increase risk for falls & frailty, suggest consideration for limiting use of these drugs.
6. Cognitive Impairment in PLWH & women with HIV in WIHS, in the UK, links to several studies below.
7. Feminizing hormones therapies & cardiovascular disease risks for transgender women.
8. For the first time except perhaps for a statin researchers identified & charaxeristized in early preliminary study that using GLP-2 agonist in PLWH reduced inflammation & improved intestinal gut barrier.
9. take #8 together with study reported at CROI listed below associating gut micriobia & cardiovascular disease & HIV.
10. Predictors of health related QOL, quality of life - included objective measured cognitive impairment, physical function, mental health & perceived control of cognitive impairment. !!!!
With the potential adverse cardiovascular effects of newer antiretroviral therapy (ART), such as integrase inhibitors and weight gain and Tenofovir Alafenamide and elevated lipids, it is critical to continue monitoring trends in myocardial infarction (MI) rates by HIV status.
Subjects included people with HIV (PWH) from two health system cohorts: Massachusetts General Hospital (Partners) and Kaiser Permanente Northern California (KPNC), identified from 2005-2017 with follow-up through 2020.
Among PLWH & people without HIV with similar risk profiles at baseline, we observed no difference in MI risk for baseline years 2005-2009, and a 60% higher risk in PLWH for years 2010-2017. Results appear driven by decrease in MI risk for people without HIV, that was not seen fir PLWH.
"HIV-specific risk factors, such as longer HIV duration & newer ART (e.g. INSTIs), may have prevented PLWH from realizing the same improvements in MI risk for people without HIV. Clinical implications for PLWH include continued surveillance for CVD & primary prevention, including possibly more aggressive interventions."
CROI: Trends in Myocardial Infarction Risk by HIV Status in Two US Healthcare Systems - (02/14/22)
Persistent immune activation and downstream macrophage-specific arterial infiltration are thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH) on ART. We applied a novel macrophage-specific imaging modality to investigate macrophage-specific infiltration among participants with vs without HIV in relation to atherosclerotic plaque and immune activation..
These data applying a novel imaging modality provide unique evidence of macrophage-specific arterial inflammation among PWH on ART, which relates specifically to non-calcified plaque. Additionally, we characterize key immune pathways relating to increased arterial inflammation of relevance to identifying novel immunomodulatory therapies for CVD reduction.
CROI: Macrophage-specific arterial infiltration relates to plaque type and immune activation in HIV - (02/14/22)
these data may suggest a potential role of this pathway in subcutaneous adipose tissue fibrosis and insulin resistance in treated HIV..
People with HIV (PWH) are at increased risk for type 2 diabetes (T2D), which has been linked to persistent inflammation despite ART. PWH have also been reported to have increased adipose tissue fibrosis, which has also been linked to insulin resistance, but the inflammatory pathways most closely linked to incident T2D and adipose tissue fibrosis in this setting remain unclear. Many inflammatory pathways, including the kynurenine pathway of tryptophan catabolism, predict incident T2D in treated HIV infection. PWH also have abnormally high SAT fibrosis. Higher IL-6, IL-18, IP-10, sCD163, suPAR, sTNFR2 and kynurenine-to-tryptophan (KT ratio) were associated with incident T2D (Figure)....
CROI: PLWH Have Higher levels of Fat Tissue Fibrosis - INFLAMMATION AND KYNURENINE PATHWAY LINKED TO TYPE 2 DIABETES AND FAT FIBROSIS IN HIV - (02/14/22)
Over 1/3 reported functional impairment. Physical function impairments occur earlier in people with HIV.
A global analysis (REPRIEVE Study) of people with HIV infection found 28% of participants had some functional impairment, 8% had moderate impairment, and fewer than 0.5% had severe impairment. Diverse studies found that functional impairment begins at a younger age in people with HIV. But little is known about differences in functional impairment by global region, gender, or antiretroviral therapy (ART) regimen.
The 7736-person analysis found significant differences in self-reported function; for example, the worst function occurred in South Asia (India) and the best in adjacent Southeast/East Asia (Thailand).
- Black race (higher income areas only), older age, identifying as female, and longer ART duration were also identified risks
Functional impairment was associated with cardiometabolic risk. WAIST Circumference was associated with impairment & severe impairment.
- DASI may provide an estimate of cardiometabolic risk; longitudinal associations will be investigated in ongoing REPRIEVE follow-up.
- Other variables significantly associated with physical function: cisgender women and"across the transgender spectrum" independently had worse function than cisgender men; function proved independently worse with each added 5 years of age compared with 40-44 (see graph showing stepwise worsting with age & 60+ the worst !!!) ; obese (BMI) people independently had worse function than overweight or normal-weight people; current and former smokers independently had worse function than never-smokers; people with longer ART duration independently (10+ yrs worse than 5, 5 worse than <5) had worse function than those with fewer than 5 years of ART; people who took a protease inhibitor or an integrase inhibitor regimen independently had worse function than those who took a nonnucleoside regimen; longer thymidine analogue exposure of 10 years or more was associated with functional impairment; and in high-income countries blacks or African Americans independently had worse function than whites.
CROI: Geographical Differences in Fnctional Impairment of PLWH: Over One Third in Global HIV Analysis Have Impaired Physical Function - (02/14/22)
Researchers working with the UK/Ireland POPPY cohort noted that clinicians prescribe anticholinergics to treat mental health conditions, bladder trouble, or allergies-all concerns common to an aging HIV population. Side effects can include dry mouth, urinary retention, and constipation. This POPPY study set out to see if taking anticholinergics affects frequency of two age-related problems-falls and frailty.
Analysis of 699 older people with HIV linked use of two or more anticholinergic drugs to 3.6-fold to 4.5-fold higher odds of recurrent falls and to doubled odds of frailty [1]. Findings reflect similar prior results in the general population.
After statistical adjustment for demographic, lifestyle, and clinical factors, any anticholinergic almost doubled odds of recurrent falls in an association that stopped short of statistical significance (odds ratio [OR] 1.9, 95% confidence interval [CI] 0.9 to 4.0, P = 0.08). The same analysis tied any anticholinergic use (nonsignificantly) to 70% higher odds of frailty (OR 1.7, 95% CI 0.9 to 3.0, P = 0.08).
the researchers stressed that their findings echo studies of anticholinergic associations in general populations worldwide, so they suggested clinicians consider these potential anticholinergic impacts and lower use of these drugs when possible.
CROI: Two or More Anticholinergics Tied to Falls, Frailty in People With HIV - (02/14/22)
Analysis of 699 older people with HIV linked use of two or more anticholinergic drugs to 3.6-fold to 4.5-fold higher odds of recurrent falls and to doubled odds of frailty [1]. Findings reflect similar prior results in the general population.
CROI:GUT MICROBIOTA, PLASMA METABOLOMICS, AND ATHEROSCLEROSIS IN HIV INFECTION (02/15/22)
Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.
CROI: IMPROVING INTESTINAL BARRIER USING GLP-2 AGONIST REDUCES ARTERIAL INFLAMMATION IN PWH
Amelioration of the intestinal epithelial barrier with teduglutide decreased arterial inflammation, activated monocytes, and CD8+ T-cells. Teduglutide-treated participants also showed increase in plasma KA, a metabolite with anti-inflammatory effects. This proof-of-concept study provides support for future research investigating intestinal epithelial integrity as a target for reduction of immune activation and cardiovascular disease in PWH. There were GI side effects.
CROI: PREVALENCE OF ANEMIA AND RISK FACTORS IN PEOPLE WITH HIV IN THE MODERN ART ERA - (02/14/22)
Using the NA-ACCORD, we estimated the annual prevalence between 01/01/2007-12/31/2017 of mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL) and severe (<8.0g/dL) anemia in PWH.
Despite decreasing over time, the prevalence of anemia among PWH is higher than that reported in the general population of high-income countries (∼5%). There was a higher burden of anemia in PWH seen among those with low CD4 counts, emphasizing the importance of effective ART.
Among 84,119 PWH, over the study period, 41,964 (49.9%) had at least one measure of anemia with 20,379 (24.2%) having mild anemia, 14,936 (17.8%) moderate anemia and 6,649 (7.9%) severe anemia.
• The average annual prevalence of anemia was 29.1% over the study period, this decreased from 2007 to 2017 (see shaded area plot).
• The risk of moderate/severe anemia was higher in females, Non-Hispanic Black and Hispanic PWH compared to Non-Hispanic White PWH, those underweight, with comorbidities and low CD4 counts (see bar charts and table).
• Aging increased anemia risk among males, but not females (see table).
CROI: IS THERE A ROLE OF NOVEL ART REGIMENS IN THE DECLINING PREVALENCE OF HAND? HAND 22% Today in Italy- Asymptomatic Remains Prevalent 10%-24% - (02/22/22) nadir CD4 associated with HAND risk & viral suppression as well
In this late cohort of ART-treated PLWH, mostly virologically suppressed, we found an overall prevalence of HAND of 22%, in line with the estimates reported in studies of participants with controlled HIV infection.
Over the last decade, a remarkable decreasing prevalence of HAND was observed in the entire population and after stratifying patients according to age, the mode of transmission, nadir CD4 cell count & viro-immunological status at NPA.
ANI (asymptomatic neurocognitive impairment) remains prevalent as compared to symptomatic stages (MND & HAD), during the entire period of observation. A reduced risk of HAND was observed with dual & INSTI-based regimens along with more recent AR. These results reflect the multifactorial pathogenesis of HAND, even in a successfully treated population & could suggest a potential role of new treatment strategies in the decline, due to their greater virological efficacy & better tolerability.
Factors associated to HAND were nadir CD4, older age, lower educational level, lower current CD4+count and HCV co-infection; CD4 >700 had least risk. Compared to pts receiving a NNRTI, those receiving dual and INSTI-based therapies were associated to a decreased risk of having HAND. To be tested in more recent years significantly predicted a reduced risk of HAND (Tab.2).
In 791/2,383 (33%) tests a cognitive complaint was reported and HAND prevalence was 40%, higher than among not-complaining (13%). Over the study period, a decreasing frequency of HAND was found in the entire population (Tab.1). Factors associated to HAND were older age, lower educational level, lower current CD4+count and HCV co-infection. Compared to pts receiving a NNRTI, those receiving dual and INSTI-based therapies were associated to a decreased risk of having HAND. To be tested in more recent years significantly predicted a reduced risk of HAND (Tab.2).
CROI: Assessing health-related quality of life in people with HIV and cognitive issues - (02/13/22) cognitive impairment, and physical function, mental health & perceived control over cognitive impairment predict health QOL.
We selected and examined a comprehensive set of domains measures that capture health-related quality of life (HRQoL) in people living with HIV and cognitive issues. This allows clinicians to target care to address the factors driving HRQoL, focus care on individual needs, follow changes over time, and quantify interventions.
HIV patients with subjective cognitive concerns (based on European AIDS Clinical Society guidelines) were identified from two clinics in London and Brighton (UK) and invited to complete a brief cognitive assessment (MoCA-Blind) and an in-person or online series of validated questionnaires measuring nine domains identified from a prior qualitative study as comprising HRQoL in PLWH with cognitive impairments. These included: physical function (Lawson and Brody Instrumental Activities of Daily Living), cognition (MoCA-Blind), social connectedness (Social Connectedness Scale), physical and mental health and wellbeing (SF-12), HIV stigma (Stigma Scale for Chronic Illness), self-esteem (Rosenburg’s Self-Esteem Scale), acceptance of health (Acceptance of Illness Scale) and control over health outcomes (Illness Perception Scale).
We explored cut-off scores which revealed a significant proportion of patients scored outside the desired range on single domains (between 33 and 79.6%), and many patients on multiple domains (40.8% on 4 or more domains). Multiple regression revealed presence of objective cognitive impairment (based on MoCA-Blind cut-off score ? 18) significantly predicted HRQoL score (R² = 0.14, F(1, 91) = 15.15, p < 0.001), and adding the remaining HRQoL domains explained 56% of the variance in HRQoL score (R² of 0.56, ?R² = 0.41 F (8,83) = 11.76, p < 0.001), with physical function, physical health, mental health, and perceived control over CI the strongest predictors (p < 0.05).
CROI: COGNITIVE PREDICTORS OF EVERYDAY FUNCTIONING IN THE WOMEN'S INTERAGENCY HIV STUDY - (02/12/22) motor function was associated with impaired IADL - independent activities of daily living, functioning.
motor function is - any activity that results from stimulation of motor neurons, including glandular activity as well as reflexes and voluntary and involuntary muscle contractions.
Nearly 30% of people with HIV experience an impairment of cognition that can interfere with performing instrumental activities of daily living (IADL). We examined cognitive performance in women with HIV (WWH) and HIV-uninfected women from the Women’s Interagency HIV Study (WIHS) to determine the relationship between cognitive function across seven cognitive domains and self-reported IADL.
Among all participants, motor function was the main cognitive domain showing an impaired IADL. Poorer motor function was associated with poorer function in getting where you need to go (P<0.001), dressing (P=0.001), home repairs (P<0.001), housekeeping (P<0.001), cooking (P=0.001), and laundry (P<0.001). In women <50 years (younger), poorer motor function was associated with poorer function in getting where you need to go (P=0.007), cooking (P=0.003), and home repairs (P=0.009). In women >50 years, motor function was associated with poorer function in getting where you need to go (P=0.006), home repairs (P=0.001), housekeeping (P=0.003), and laundry (P=0.002). Among WWH, poorer motor function was associated with poorer function in dressing (P=0.01), home repairs (P<0.001), housekeeping (P=0.001), and laundry (P=0.009), and was driven by older WWH. Moreover, poorer executive function was associated with reduced ability to plan social activities (P=0.007).
CROI: Abnormal cognitive aging is detected despite clinically defined cognitive stability - (02/12/22)
Thirty one percent (n=142) were classified as cognitively impaired at baseline. At Month-12 and Month-24, 6% and 7% of the sample showed clinically-relevant cognitive decline and 4% and 3% improved respectively (Figure 1).
Australia has surpassed the UNAIDS targets of 90% ART coverage and viral suppression among treated people living with HIV (PLHIV). This national HIV treatment success provides us with a unique context to study cognitive trajectories, cognitive aging, and a comprehensive set of health, social and lifestyle factors that may influence cognition during chronic and stable HIV disease
CROI: Decreased Myelin Content and Cognitive Performance in Adults with Perinatal HIV - (02/13/22)
CROI: PETRAM RESULTS: BONE TURNOVER CHANGES ON 18F-NaF PET/CT AFTER A RANDOMISED SWITCH TO TAF - (02/13/22)
CROI: IMPACT OF INTEGRASE STRAND TRANSFER INHIBITORS ON COGNITION IN THE HAILO COHORT - (02/12/22)
CROI: FEMINIZING HORMONAL THERAPIES WORSEN CARDIOMETABOLIC PROFILES IN TRANSGENDER WOMEN - (02/12/22)
NATAP reports, coverage:
CROI
Conference on Retroviruses
and Opportunistic Infections
Virtual
February 12-16, 2022
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